Implementation of sentinel lymph node biopsy for breast cancer by surgeons in the Department of Defense

BACKGROUND: Sentinel lymph node biopsy (SLNB) for the evaluation of women with invasive breast cancer is rapidly gaining acceptance. The purpose of this study was to assess how surgeons in the Department of Defense (DOD) are incorporating SLNB into practice. METHODS: Surgeons at all DOD hospitals were telephonically surveyed regarding their current practices with SLNB. RESULTS: Of 66 DOD hospitals 23 (35%) are currently performing SLNB. Eleven hospitals (11 of 23, 48%) are academic centers, while 12 (12 of 23, 52%) are not teaching facilities. Seventeen (17 of 23, 77%) are in the learning phase of SLNB and follow SLNB with an axillary dissection. Eighteen (18 of 23, 78%) of facilities have surgeons who learned the procedure in residency/fellowship training. Sixteen (16 of 23, 70%) use a combination of isosulfan blue dye and sulfur colloid radioisotope. Surgeons performing SLNB are not aware of the method of examination of the sentinel node at their institution at 6 of 23 (26%) of hospitals. CONCLUSIONS: Increasing numbers of surgeons in the DOD Healthcare System are performing SLNB. The majority learned the procedure in residency or fellowship and are using a combination of blue dye and radioisotope for the performance of SLNB.     

Novel germline c-MET mutation in a family with hereditary papillary renal carcinoma

Hereditary papillary renal carcinoma (HPRC) is a highly penetrant hereditary renal cancer syndrome caused by germline missense mutations in the c-MET proto-oncogene. HPRC is clinically characterized by multiple bilateral papillary renal-cell carcinomas. Here we report a family with a novel missense mutation in c-MET. The original pathology report of four primary kidney cancers (1988–1997) revealed renal-cell carcinoma. A revised report described multiple adenomas and papillary renal-cell carcinomas with focal clear cells and a mixture of type 1 and type 2 pattern, emphasizing the importance of revised pathology examinations in possible hereditary renal-cell carcinomas especially when described before 1997.     

Targeting JNK-interacting protein 1 (JIP1) sensitises osteosarcoma to doxorubicin

Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. Despite aggressive therapy, survival outcomes remain unsatisfactory, especially for patients with metastatic disease or patients with a poor chemotherapy response. Chemoresistance contributes to treatment failure. To increase the efficacy of conventional chemotherapy, essential survival pathways should be targeted concomitantly. Here, we performed a loss-of-function siRNA screen of the human kinome in SaOS-2 cells to identify critical survival kinases after doxorubicin treatment. Gene silencing of JNK-interacting-protein-1 (JIP1) elicited the most potent sensitisation to doxorubicin. This candidate was further explored as potential target for chemosensitisation in OS. A panel of OS cell lines and human primary osteoblasts was examined for sensitisation to doxorubicin using small molecule JIP1-inhibitor BI-78D3. JIP1 expression and JIP1-inhibitor effects on JNK-signalling were investigated by Western blot analysis. JIP1 expression in human OS tumours was assessed by immunohistochemistry on tissue micro arrays. BI-78D3 blocked JNK-signalling and sensitised three out of four tested OS cell lines, but not healthy osteoblasts, to treatment with doxorubicin. Combination treatment increased the induction of apoptosis. JIP1 was found to be expressed in two-thirds of human primary OS tissue samples. Patients with JIP1 positive tumours showed a trend to inferior overall survival. Collectively, JIP1 appears a clinically relevant novel target in OS to enhance the efficacy of doxorubicin treatment by means of RNA interference or pharmacological inhibition.     

The Impact of Mitral Stenosis on Left Atrial Function Assessed by Two‐Dimensional Speckle Tracking Echocardiography

Aims: The aim of this study is to investigate the effect of mitral stenosis (MS) on left atrial (LA) function using two‐dimensional speckle tracking echocardiography (2DSTE). Methods and Results: The study subjects consisted of 52 patients with asymptomatic MS and 52 control subjects. LA function was assessed using prototype speckle tracking software and manual tracking method. Maximal LA volume (LAVmax) and minimal LA volume (LAVmin) and LA volume before atrial contraction (LAVpre‐a) were measured. Using these volumes, LA reservoir, conduit and booster pump fuction parameters were calculated. Indexed LAVmax, LAVmin, and LAVpre‐a measurements via speckle tracking were highly correlated with manual tracing methods in both groups. Expansion index (67.8 ± 36.4 vs. 148.3 ± 44.2), diastolic emptying index (37.7 ± 12.9 vs. 58.0 ± 8.5), passive emptying (37.3 ± 14.1 vs. 70.4 ± 10.4) and passive emptying index (13.3 ± 6.3 vs. 41.3 ± 10.6) were decreased significantly in MS patients (P < 0.001). In contrast active emptying index (62.6 ± 4.1 vs. 29.5 ± 10.1) increased in MS group (P < 0.001) while active emptying (28.1 ± 13.0 vs. 28.3 ± 6.9) remained same among both groups. Conclusions: This is the first study relating LA volumes and function assessed by 2DSTE to MS. 2D speckle tracking analysis of LA volume is relatively easy and provides more detailed information regarding the changes in LA volumes during the cardiac cycle.     

Determinants for a low health-related quality of life in asthmatics

People with asthma suffer from impaired health-related quality of life (HRQL), but the determinants of HRQL among asthmatics are not completely understood. The aim of this investigation was to study determinants of low HRQL in asthmatics and to study whether the determinants of HRQL differ between sexes and age groups. A cohort of three age groups in Sweden was investigated in 1990 using a questionnaire with focus on respiratory symptoms. To study quality of life, the generic instrument Gothenburg Quality of Life was used. The participants were also investigated with interviews, spirometry, and allergy testing. Asthma was diagnosed in 616 subjects. Fifty-eight per cent (n = 359) of the subjects were women; and 24% were smokers, 22% ex-smokers, and 54% were non-smokers. Women were more likely than men to report poor health-related quality of life. Respiratory symptoms severity was another independent determinant of a lower quality of life as well as airway responsiveness to irritants. Current and former smokers also reported lower quality of life. Finally, absenteeism from school and work was associated with lower quality of life. Factors such as sex, smoking habits, airway responsiveness to irritants, respiratory symptom severity, allergy, and absenteeism from school and work were associated with low HRQL in asthmatics.     

Increasing organ donation via changes in the default choice or allocation rule

This research utilizes a laboratory experiment to evaluate the effectiveness of alternative public policies targeted at increasing the rate of deceased donor organ donation. The experiment includes treatments across different default choices and organ allocation rules inspired by the donor registration systems applied in different countries. Our results indicate that the opt-out with priority rule system generates the largest increase in organ donation relative to an opt-in only program. However, sizeable gains are achievable using either a priority rule or opt-out program separately, with the opt-out rule generating approximately 80% of the benefits achieved under a priority rule program.